The Science Of Fat Cells: Losing Weight, Gaining Weight, Killing Fat Cells, Liposuction, Body Contouring, CoolSculpting®, ECM Remodeling, And More!

THE LIFE OF A FAT CELL

When it comes to adipose tissue (aka: “fat cells”), what should arguably be a love/love relationship, has quickly morphed into a hate/hate one. At its core, a fat cell valiantly intends to store excess energy to combat energy toxicity and prep us for times of potential starvation. Yet in our current over-fed, sedentary society, these fat cells often become stubborn storage units you can never quite seem to clean out. 

And while it may seem like conscious willpower plays the primary role in any weight we lose or gain in a given day, our fat cells themselves are likely a largely influential - if not deciding - factor in our body’s seeming preference for a certain weight. The average human has around 30 billion fat cells, though that number can reach in the hundred billions for people struggling with obesity. Far from benign storage depots, fat cells actually act as entire endocrine organs, stimulating appetite-raising hormones like ghrelin, and appetite-suppressing hormones like leptin. They also signal to the hypothalamus (the master hormone regulator in the brain) to maintain a certain body fat weight, thought of as the “body set point.” 

It’s this seeming set point which can cause angst in many a disillusioned individual, inciting a brimming  - and often highly effective - body contouring industry.

Types Of Fat

Fat cells contain stored energy in the form of triglycerides, which are composed of free fatty acids bound to glycerol. There are three basic types of fat stores determined by location, as well as three basic types of the actual fat itself. On the geographical side of things, subcutaneous fat is stored beneath the skin – residing between the skin and the muscle - and often accumulates around pinchable areas like the arms and love handles. Accounting for an average 80% of total body fat, subcutaneous fat tends to be around 15-20% of a man’s body weight, and 20-25% of a woman’s weight.

While many people find subcutaneous fat aesthetically displeasing, it is actually correlated to better health, when it composes a higher ratio of total body fat. The more silent and hidden visceral fat, on the other hand, is known as “the dangerous” type of fat, stored around internal organs. Lastly, ectopic fat may be the crème de la crème of problematic adipose tissue, as it is a type of fat that accumulates inside internal organs, like the muscles, heart, and liver.

Besides physical location, the type of fat itself can be white, brown, or beige. White adipose tissue is the "stubborn" type of fat that functions for storage and insulation, and is often a chief contributor to health issues. Brown fat, on the other hand, is a sort of magical fat that we actually want more of. Rich in mitochondria, brown fat actually burns energy to generate heat, meaning it can help maintain a healthier figure! To generate more brown fat, you can turn to modalities such as cold exposure. And want some good news? White fat can actually transform into brown fat, with “beige” fat being an in-between type of fat in the transition.

Birthing Fat

Is a fat cell just a fat cell?

The mechanism of weight gain and loss is typically attributed to shrinking and growing fat cells, with the fat cell’s volume changing based on the amount of fatty acids held within the cells. When they reach max capacity, fat cells can even split to form new fat cells (which we are often warned we will never lose. More on that in a bit.)

Interestingly, the ease with which fat cells form new fat cells correlates to metabolic health potential – but in the opposite of what might be expected. Easier weight gain can actually be metabolically protective in the short term, since energy toxicity may be a primary driver of disease. In situations of overfeeding, those who are genetically resistant to forming new fat cells (known as “restricted hyperplasia”) enter a situation in which normally protective fat cells, rather than splitting and forming new fat cells to accommodate the influx in energy, instead allow fatty acids to spill over into the blood stream. This leads to accumulation of fat in areas and organs not suited for such, exacerbating metabolic disease and disorders. These overly stretched fat cells also increase inflammatory potential by releasing cytokines, and experience an extracellular matrix (ECM) which encourages the body to regain the weight (more on that in a bit as well!)

Dying Fat

A prevalent idea exists that fat cells never die – once a fat cell, always a fat cell, and even if you successfully “empty your” fat cells, the cell itself never dies. As it turns out, things are likely far more complicated than “fat cells never die” – though for all intents and purposes, this may manifest as truth in practicality.

Indeed, studies consistently find our number of fat cells tends to remain stubbornly constant throughout adulthood, with the “number” seemingly set in childhood. Even in bariatric surgical treatments which result in decreased BMI of around 18 points thanks to stapling the stomach, the same actual number of fat cells tend to remain the same two years after the procedure, though the fat cells themselves have shrunk substantially. 

But are these the same fat cells? That, my friends, is the burning question.

Historically, fat cells have resided in a dark hole in nutritional science, due to their extreme difficulty and safety to analyze. While labelled nucleotides are used to track fat cells in rodent studies, these tagging methods cannot be implemented in human trials due to toxicity. Insight into the fat cell mystery arose with the discovery of a sort of carbon dating for fat cells!

In 2008, Kirsty Spalding at the Karolinska Institute in Sweden discovered a method for tracking the lifespan of fat cells, thanks to the traceability of a carbon compound called 14C: a radioactive isotope which spread across the globe due to nuclear testing in the 1950s. Levels of 14C rose from 1955 until 1963, at which point levels declined due to the Nuclear Test Ban Treaty. Since 14C converts into carbon dioxide in the atmosphere, it was taken up by plants and made its way into the food supply. Levels of 14C accumulated in genomic DNA of fat cells, meaning fat cells reveal their sort of “birth date,” based on their levels of 14C.

Through the study of the radioactive isotope 14C, it has been found that approximately10% of fat cells are turned over annually, with around half of fat cells replaced every 8.3 years. By analyzing the fat tissues of individuals born before and after the Cold War, Spalding found that people’s fat cells tended to be about 20 years or younger than themselves. This implies that – while the number of fat cells remains eerily constant – fat cells are in fact dying and being reborn. Spalding also found that obese children tend to add fat cells at double the rate of their lean counterparts, with the body trying to maintain that number throughout adulthood.

It would seem that fat cells are born and die, yet some governing hormonal factors (likely in the hypothalamus) work to control that number. You may seem like you are destined to a certain number of fat cells – and perhaps in a way you are – but those fat cells are still changing.

The benefits of liposuction, and other modalities discussed below, may also include the ability to target stubborn fat cells resistant to shrinking and/or dying. Which brings us to…

ECM Remodeling

You’d think the most authoritative part of a fat cell would be its nucleus, which harbors the fat cell’s DNA. However, the most influential part of a fat cell is likely its outer membrane and extracellular cellular matrix, or “ECM.” For a super deep dive into the ECM and fat cell remodulating, I suggest checking out Joel Greene’s The Immunity Code (who I had on an episode of The Melanie Avalon Biohacking Podcast.) But here’s the long story short.

 A cell’s membrane serves as the barrier for all fuel entering and exiting the cell, as well as the port for hormonal receptors, which affect inflammatory signaling and interact with the hypothalamus for appetite and weight regulation. The ECM serves as the structure literally holding the cell together – like the framework of a house.

It is the mechanical set up of the ECM which may be a key driver in the need to regain weight. This is because when fat cells lose their contents, the outer structure (ECM) needs to be remodeled to accommodate the fatty acid loss in the cells. Otherwise, the ECM causes an actual mechanical stress in the cell.

You can think about it like if you lost or gained weight, and the effects on your clothes. When you lose weight, they are baggy and misshapen. Since fat cells can’t just buy a new ECM like you can buy a new outfit at the store, they instead have two options: spend the time and energy to remodel the ECM to “fit” the new cell (like altering or taking in your clothes), or simply fill the cell back up with fat, to make the clothes fit again. Which do you think the body “prefers” to do, out of ease? (Hint: Your body tends to be down with regaining weight.)  

Another problem besides the difficulty of remodeling the ECM, is that every time the cells lose and gain fat, it causes the ECM to become stiffer and stiffer, making it harder and harder to lose weight in the future, and creating a more inflammatory state. This is a cellular reason for why yoyo dieting is so detrimental.

FAT REMOVAL OPTIONS

For a myriad of hormonal, diet, and lifestyle reasons, burning fat can be a difficult if not illusory goal. When fat cells don’t respond to diet and exercise, literally removing fat cells from the body through mechanical methods can be a viable method when others seem to fail. Here’s a brief overview of the options, what you can expect, and the risks and benefits. Note that all of these methods target subcutaneous fat, rather than visceral fat, and many methods are intended more for “contouring,” rather than weight loss per se.

Traditional Liposuction

Traditional liposuction is an invasive procedure requiring anesthesia, and is the most common cosmetic procedure performed worldwide. Commonly targeted areas include the abdomen, love handles, flanks, hips, inner thighs, and buttocks. The amount of fat removed can range from around 1,000ml to up to around 5,000 ml (the equivalent of 11 pounds of fat). Technically, there is no actual upper limit, though the risk of aesthetic complications and water imbalances increases, the more fat that is  removed.

In traditional liposuction, incisions are made into the skin, and a long thin hollow tube (cannula) is inserted to dislodge fat, which is then sucked out via a syringe attached to the cannula, or through a surgical vacuum. The procedure leaves a scar, and the most common post-op issue is contour deformity, characterized by folds and wrinkles. Skin may not retain firmness or elasticity after, leading to a draping effect. Good candidates for liposuction therefore have skin high in elasticity, with a BMI that is around 20-30% of their ideal body weight.

Compared to other surgical procedures, the procedure itself is short (usually less than 3 hours), and the recovery is also short compared to other conventional surgeries, with few complications reported, and low morbidity and mortality rates. Recovery involves wearing a compression garment suit to help the skin remodulate. (Do not underestimate the unpleasantness of this.)

Potential complications include skin discoloration, fluid retention, surgical site infection, and localized bleeding. While inflammatory markers are transiently elevated post-surgery, there do not tend to be lasting inflammatory effects. On the contrary, the removal of fat stores may lead to increased health benefits associated with weight loss.

A 2012 study of 301 patients, found the average weight loss from lower body liposuction tends to be around 2.2 lbs., increasing to 4.6 lbs. when abs are also targeted. Studies also show liposuction does indeed significantly reduce thigh, abdominal, knee, and arm width. (Beyond just removal, some opt for fat transfers, in which the removed fat is inserted somewhere else – such as into the butt or breasts, like the “Brazilian butt lift.”)

Are the results from liposuction permanent?

The fat cells removed from liposuction are, indeed, gone. They do not come back, leading to long term effects. Especially if these were “stubborn” fat cells resistant to being burned due to hormonal factors, liposuction can be a viable option for making lasting compositional changes to one’s body. That said, one can of course regain weight by filling other fat cells, and there is always the potential for new fat cell creation in a state of overfeeding. Those who regain weight after liposuction, may gain it in different places.

OTHER LIPOSUCTION METHODS

Researching laser, ultrasound, and radiofrequency can be a bit confusing, as a multitude of devices and methods exist. These devices can be used independently without any mechanical removal of fat cells, or in conjunction with suction, in a method more similar to traditional liposuction, yet with local anesthesia only. The majority of my focus here will be the later, assisted-liposuction method.

Laser Liposuction

A less invasive yet comparable alternative to liposuction, laser liposuction has risen in popularity over the past years. Performed under local anesthesia (with patients often given a combination of antianxiety and pain killers prior), small incisions are made in the treatment areas. A laser is then used to liquify the fat cells, by rupturing the fat cell’s membranes. Some procedures stop with that, while the more traditional form sucks out the fat via a cannula (similar to traditional liposuction). The laser is also purported to help remodel the surrounding collagen and dermis.

Some surgeons close the wounds, while others leave them open. Open wounds allow for more draining, and thus potentially faster healing – although patients can expect to “leak” for a few days, up to over a week.

Recovery involves wearing a compression garment and suit to help the skin remodulate. (As mentioned before, do not underestimate the unpleasantness of this). While uncommon, complications can include burns from the laser. (A 2017 study found this happened in around 5% of cases.)

Ultrasound-Assisted or Radiofrequency Liposuction

Both ultrasound or radiofrequency (RF) energy can be used to generate a thermal effect, rupture and liquify fat cells.  Commonly treated areas using these modalities include arms, thighs, hips, and buttocks.

In methods like traditional liposuction, a rod is inserted into the skin through incisions to deliver the ultrasound energy. If used noninvasively, the killed fat cells are processed by the body over the next few weeks. (As of 2016, radiofrequency devises were the most popular non-invasive therapies.) The more traditional approaches like liposuction, remove the ruptured fat through suction, via a canula. Studies indicate that treatment with ultrasound results in increased free fatty acids in the bloodstream, as well as norepinephrine, which may play a role in mobilizing the fatty acids.  

Despite its popularity for lipolysis, there are only a few studies on its efficacy and safety. However, the treatments typically result in minimal, if any discomfort – with potentially mild erythema and edema. Results can also be less  predictable than traditional liposuction.

Injection Lipolysis

In injection lipolysis (like Kybella), cocktails made of phosphatidylcholine and/or deoxycholate are injected into the body to help dissolve fat cells. Originally used to treat atheroma plaques in cardiac disease, phosphatidylcholine is created from soybean lecithin, while deoxycholate is a bile salt,  originally used as a laboratory detergent. The compounds can be used individually or together, and stimulate lipolysis by encouraging fat cells to split into fatty acids and glycerol. While the compounds can be applied topically as lotions or creams, the injections are potentially more effective.

Injection lipolysis can be used as a stand-alone treatment, or as a “touch-up” after more traditional liposuction methods. The most commonly treated areas include the face and bra roll, with more modest effects in the arms and larger areas.

Injection lipolysis side effects tend to be minor, and include stinging, pain, fluid retention, and edema, erythema, and a stinging sensation. These typically decline within hours, to 2–3 days after the procedure.

CoolSculpting®

On the flip side of attacking fat through thermal heating methods, cryolipolysis comes from words meaning “cold fat destruction.” Known colloquially as "fat freezing", and the brand “CoolSculpting®,” this noninvasive procedure uses extreme cold temperatures to kill subcutaneous fat cells, which are then eliminated by the body over a few months. (CoolSculpting®  is not typically combined with suction liposuction methods like those discussed above.)

Just how cool sculpting works is up for debate, but researchers hypothesize that fat cells are more prone to injury to extreme temperatures, unlike their neighboring water-based cells, which creates a sort of selective targeted killing of fat cells. By applying the freezing temperatures, the fat cells are damaged and die within a few days. Over the next 90 days or so, the body then cleans up shop via inflammatory macrophages, which basically eat up dead and non-functioning cells. Studies have found the influx of inflammatory markers increase two weeks after treatment, but decline after a month, and continue to dwindle 3 months after treatment.

CoolSculpting® is cleared for the love handles, thighs, belly, bra fat, back, buttocks, arms, and chin.  In the procedure, a vacuum device suctions the skin, and applies temperatures of -11 degrees Celsius. While the patient may initially experience a cold sensation, the area typically goes numb and provides little discomfort during the session. The area is usually massaged afterwards to improve the homogeneity of the area. Perhaps surprisingly, it is this massage process which is often reported to be the most painful part of the process.

A November 2018 study published in Dermatology Research and Practice,  contrast cryolipolysis to be “safe and effective in reducing the fat layer and improving body contouring.” Interestingly, patients with the procedure tend to experience reduced waist measurements and skinfold, but little change (if any) in weight or BMI. Similar to traditional liposuction, it is recommended to be close to ideal body weight before undergoing cryolipolysis: it is more for fine tuning and spot treating, rather than overall fat/weight reduction. Average reduction in fat ranges from about 10% to 25% per round of treatment in the area, and after 3-4 months, a second treatment in the same areas may be required to achieve desired results.

The ideal candidates for CoolSculpting® include those close to their ideal body weight, who want to address particularly stubborn areas resistant to dietary and exercise interventions. Benefits of CoolSculpting® include very little downtime, if any. Studies tend to confirm no measurable related changes in health-related blood markers, though side effects include redness, numbness, and tingling. Lingering aesthetic effects can be a subtle darkening of the skin, and some users report a lasting numbness in the area.

FAT REFLECTIONS

One cannot deny that the environmental factors of today’s diet and lifestyle have rendered our fat cells often obstinate obstacles. The more I research the inflammatory effects which can happen to fat cells with substantial weight gain - or even smaller weight gain but in yoyo pattern – the more physically removing the cells through surgical methods may seem like a viable option for many. Especially if someone has a personal preference to remove especially stubborn deposits, removing them via the above methods may be more alluring than restrictive diets or exercise.

Of course, one should consider the cost/benefits of “instant” fat removal, with the traumatic process of surgery to the body, as well as potentially lingering effects such as scar tissue or uneven contouring. The compression suit recovery process should also be taken into account: some surgeons recommend wearing the tight clothing daily for up to 6 months! And with anything, expectation management is key to choosing the best method.

The implications of the relatively recently discovered 10% annual fat cell turnover, also begs more research for its implication on potentials fat destruction avenues. Indeed, patients who undergo liposuction tend to experience “permanent” results of the fat loss, although subsequent weight gain may lead to weight regain in other areas. Does the normal “death” of a fat cell and subsequent turnover from "normal life" affect the body weight set point differently, compared to removing a fat cell in its entirety through surgical means? In other words, does liposuction reduce the body weight set point due to the removal of hormone-signaling fat cells? Does the body experience a decrease in appetite-raising hormones when fat cells are removed? Or, if fat cells are only partially damaged with heat or cold lipo modatlities, and not completely expelled from the body, does the fat cell begin to be refilled to alleviate the stress from the damaged ECM?  So many questions! Perhaps only further research and time will tell.

Have you done any fat-removal methods? I'd love to hear your experience in the comments below!